Generic placeholder image

Current Radiopharmaceuticals

Editor-in-Chief

ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

Research Article

Etodolac Enhances the Radiosensitivity of Irradiated HT-29 Human Colorectal Cancer Cells

Author(s): Zahra Shaghaghi, Nasim Zarei Polgardani, Sahar Abbasi, Hajar Albooyeh, Leila Dastranj, Soghra Farzipour and Maryam Alvandi*

Volume 15, Issue 3, 2022

Published on: 29 April, 2022

Page: [242 - 248] Pages: 7

DOI: 10.2174/1874471015666220321143139

Price: $65

Abstract

Background: Radioresistance is found to be the main therapeutic restriction in colorectal radiation therapy. The aim of this study was to investigate the synergistic effect of Etodolac (ET) and ionizing radiation on human colorectal cancer cells.

Methods: Pretreated HT-29 cells with ET were exposed to ionizing radiation. The radiosensitizing effect of ET was evaluated using MTT, flow cytometry, and clonogenic assay. The amount of nitrite oxide (NO) in irradiated cells was also measured with the Griess reagent.

Results: The present study found that pretreatment of HT-29 cells with ET decreases their survival and colony formation. Higher concentrations of ET cause total apoptosis and an increase in NO levels in irradiated cells.

Conclusion: Applying ET in a concentration-dependent manner had an incremental effect on the amount of apoptosis and cell death induced by radiation.

Keywords: Etodolac, radiosensitizing, colorectal cancer, apoptosis, ionizing radiation, flowcytometry.

Graphical Abstract

[1]
Yadollahpour, A.; Rezaee, Z.; Bayati, V.; Tahmasebi Birgani, M.J.; Negad Dehbashi, F. Radiotherapy enhancement with electroporation in human intestinal colon cancer HT-29 Cells. APJCP, 2018, 19(5), 1259-1262.
[PMID: 29801410]
[2]
Shaghaghi, Z.; Alvandi, M.; Nosrati, S.; Hadei, SK. Potential utility of peptides against damage induced by ionizing radiation. Future Oncol., 2021, 17(10), 1219-1235.
[PMID: 33593084]
[3]
Wu, Y.; Pu, N.; Su, W.; Yang, X.; Xing, C. Downregulation of miR-1 in colorectal cancer promotes radioresistance and aggressive pheno-types. J. Cancer, 2020, 11(16), 4832-4840.
[http://dx.doi.org/10.7150/jca.44753] [PMID: 32626530]
[4]
Jelonek, K.; Pietrowska, M.; Widlak, P. Systemic effects of ionizing radiation at the proteome and metabolome levels in the blood of can-cer patients treated with radiotherapy: The influence of inflammation and radiation toxicity. Int. J. Radiat. Biol., 2017, 93(7), 683-696.
[http://dx.doi.org/10.1080/09553002.2017.1304590] [PMID: 28281355]
[5]
Singh, N.; Baby, D.; Rajguru, J.P.; Patil, P.B.; Thakkannavar, S.S.; Pujari, V.B. Inflammation and cancer. Ann. Afr. Med., 2019, 18(3), 121-126.
[http://dx.doi.org/10.4103/aam.aam_56_18] [PMID: 31417011]
[6]
Torabizadeh, S.A.; Rezaeifar, M.; Jomehzadeh, A.; Nabizadeh Haghighi, F.; Ansari, M. Radioprotective potential of sulindac sulfide to prevent DNA damage due to ionizing radiation. Drug Des. Devel. Ther., 2019, 13, 4127-4134.
[http://dx.doi.org/10.2147/DDDT.S218022] [PMID: 31827319]
[7]
Kim, W.; Son, B.; Lee, S.; Do, H.; Youn, B. Targeting the enzymes involved in arachidonic acid metabolism to improve radiotherapy. Cancer Metastasis Rev., 2018, 37(2-3), 213-225.
[http://dx.doi.org/10.1007/s10555-018-9742-0] [PMID: 29971572]
[8]
Deorukhkar, A.; Krishnan, S. Targeting inflammatory pathways for tumor radiosensitization. Biochem. Pharmacol., 2010, 80(12), 1904-1914.
[http://dx.doi.org/10.1016/j.bcp.2010.06.039] [PMID: 20599771]
[9]
Fukuda, K.; Sakakura, C.; Miyagawa, K.; Kuriu, Y.; Kin, S.; Nakase, Y.; Hagiwara, A.; Mitsufuji, S.; Okazaki, Y.; Hayashizaki, Y.; Yamag-ishi, H. Differential gene expression profiles of radioresistant oesophageal cancer cell lines established by continuous fractionated irradia-tion. Br. J. Cancer, 2004, 91(8), 1543-1550.
[http://dx.doi.org/10.1038/sj.bjc.6602187] [PMID: 15365572]
[10]
Na, Y.J.; Kim, B.R.; Kim, J.L.; Kang, S.; Jeong, Y.A.; Park, S.H.; Jo, M.J.; Kim, J.Y.; Kim, H.J.; Oh, S.C.; Lee, D.H. Deficiency of 15-LOX-1 induces radioresistance through downregulation of MacroH2A2 in colorectal cancer. Cancers (Basel), 2019, 11(11)E1776
[http://dx.doi.org/10.3390/cancers11111776] [PMID: 31717983]
[11]
Palayoor, S.T.; Bump, E.A.; Calderwood, S.K.; Bartol, S.; Coleman, C.N. Combined antitumor effect of radiation and ibuprofen in human prostate carcinoma cells. Clin. Cancer Res., 1998, 4(3), 763-771.
[PMID: 9533546]
[12]
Bradbury, C.M.; Markovina, S.; Wei, S.J.; Rene, L.M.; Zoberi, I.; Horikoshi, N.; Gius, D. Indomethacin-induced radiosensitization and inhibition of ionizing radiation-induced NF-kappaB activation in HeLa cells occur via a mechanism involving p38 MAP kinase. Cancer Res., 2001, 61(20), 7689-7696.
[PMID: 11606413]
[13]
Goel, H.; Tikoo, K.; Arun Karpe, P.; Singla, R.; Ranjan Sinha, V. Ameliorated chemotherapeutic potential of diverse dose flouropyrimidine therapy by etodolac via NF-KB pathway, PPAR-γ expression and COX-II inhibition in DMH induced colon cancer rats. Clin. Cancer Drugs, 2016, 3(2), 109-120.
[http://dx.doi.org/10.2174/2212697X03666160118233255]
[14]
Kobayashi, M.; Nakamura, S.; Shibata, K.; Sahara, N.; Shigeno, K.; Shinjo, K.; Naito, K.; Ohnishi, K. Etodolac inhibits EBER expression and induces Bcl-2-regulated apoptosis in Burkitt’s lymphoma cells. Eur. J. Haematol., 2005, 75(3), 212-220.
[http://dx.doi.org/10.1111/j.1600-0609.2005.00498.x] [PMID: 16104877]
[15]
Nikzad, S.; Hashemi, B.; Hassan, Z.M.; Mozdarani, H. The cell survival of F10B16 melanoma and 4T1 breast adenocarcinoma irradiated to gamma radiation using the MTT assay based on two different calculation methods. J. Biomed. Phys. Eng., 2013, 3(2), 29-36.
[PMID: 25505745]
[16]
Anoopkumar-Dukie, S.; Carey, J.B.; Conere, T.; O’sullivan, E.; van Pelt, F.N.; Allshire, A. Resazurin assay of radiation response in cul-tured cells. Br. J. Radiol., 2005, 78(934), 945-947.
[http://dx.doi.org/10.1259/bjr/54004230] [PMID: 16177019]
[17]
Yoon, S.W.; Tsvankin, V.; Shrock, Z.; Meng, B.; Zhang, X.; Dewhirst, M.; Fecci, P.; Adamson, J.; Oldham, M. Enhancing radiation thera-py through cherenkov light-activated phototherapy. Int. J. Radiat. Oncol. Biol. Phys., 2018, 100(3), 794-801.
[http://dx.doi.org/10.1016/j.ijrobp.2017.11.013] [PMID: 29413289]
[18]
Seo, S.J.; Choi, H.G.; Chung, H.J.; Hong, C.K. Time course of expression of mRNA of inducible nitric oxide synthase and generation of nitric oxide by ultraviolet B in keratinocyte cell lines. Br. J. Dermatol., 2002, 147(4), 655-662.
[http://dx.doi.org/10.1046/j.1365-2133.2002.04849.x] [PMID: 12366409]
[19]
Rödel, F.; Hoffmann, J.; Distel, L.; Herrmann, M.; Noisternig, T.; Papadopoulos, T.; Sauer, R.; Rödel, C. Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res., 2005, 65(11), 4881-4887.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-3028] [PMID: 15930309]
[20]
Tang, L.; Wei, F.; Wu, Y.; He, Y.; Shi, L.; Xiong, F. Role of metabolism in cancer cell radioresistance and radiosensitization methods. J. Exp. Clin. Cancer Res., 2018, 37(1), 87.
[PMID: 29688867]
[21]
Chen, W.S.; Wei, S.J.; Liu, J.M.; Hsiao, M.; Kou-Lin, J.; Yang, W.K. Tumor invasiveness and liver metastasis of colon cancer cells corre-lated with cyclooxygenase-2 (COX-2) expression and inhibited by a COX-2-selective inhibitor, etodolac. Int. J. Cancer, 2001, 91(6), 894-899.
[http://dx.doi.org/10.1002/1097-0215(200102)9999:9999<894:AID-IJC1146>3.0.CO;2-#] [PMID: 11275997]
[22]
Laine, L.; Sloane, R.; Ferretti, M.; Cominelli, F. A randomized double-blind comparison of placebo, etodolac, and naproxen on gastroin-testinal injury and prostaglandin production. Gastrointest. Endosc., 1995, 42(5), 428-433.
[http://dx.doi.org/10.1016/S0016-5107(95)70045-5] [PMID: 8566633]
[23]
Roy, D.; Arason, G.A.; Chowdhury, B.; Mitra, A.; Calaf, G.M. Profiling of cell cycle genes of breast cells exposed to etodolac. Oncol. Rep., 2010, 23(5), 1383-1391.
[http://dx.doi.org/10.3892/or_00000775] [PMID: 20372855]
[24]
Laube, M.; Kniess, T.; Pietzsch, J. Development of antioxidant COX-2 inhibitors as radioprotective agents for radiation therapy-A hypothe-sis-driven review. Antioxidants (Basel, Switzerland), 2016, 5(2), 14.
[PMID: 27104573]
[25]
Kobayashi, S.; Nantz, R.; Kitamura, T.; Higashikubo, R.; Horikoshi, N. Combined inhibition of extracellular signal-regulated kinases and HSP90 sensitizes human colon carcinoma cells to ionizing radiation. Oncogene, 2005, 24(18), 3011-3019.
[http://dx.doi.org/10.1038/sj.onc.1208508] [PMID: 15735687]
[26]
Patsos, H.A.; Greenhough, A.; Hicks, D.J.; Al Kharusi, M.; Collard, T.J.; Lane, J.D.; Paraskeva, C.; Williams, A.C. The endogenous canna-binoid, anandamide, induces COX-2-dependent cell death in apoptosis-resistant colon cancer cells. Int. J. Oncol., 2010, 37(1), 187-193.
[PMID: 20514410]
[27]
Elder, D.J.; Halton, D.E.; Hague, A.; Paraskeva, C. Induction of apoptotic cell death in human colorectal carcinoma cell lines by a cy-clooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug: Independence from COX-2 protein expression. Clin. Cancer Res., 1997, 3(10), 1679-1683.
[PMID: 9815550]
[28]
Negi, R.R.; Rana, S.V.; Gupta, V.; Gupta, R.; Chadha, V.D.; Prasad, K.K.; Dhawan, D.K. Over-expression of cyclooxygenase-2 in colorec-tal cancer patients. APJCP, 2019, 20(6), 1675-1681.
[http://dx.doi.org/10.31557/APJCP.2019.20.6.1675] [PMID: 31244287]
[29]
Riganti, C.; Miraglia, E.; Viarisio, D.; Costamagna, C.; Pescarmona, G.; Ghigo, D.; Bosia, A. Nitric oxide reverts the resistance to doxoru-bicin in human colon cancer cells by inhibiting the drug efflux. Cancer Res., 2005, 65(2), 516-525.
[PMID: 15695394]
[30]
Cianchi, F.; Cortesini, C.; Fantappiè, O.; Messerini, L.; Sardi, I.; Lasagna, N.; Perna, F.; Fabbroni, V.; Di Felice, A.; Perigli, G.; Mazzanti, R.; Masini, E. Cyclooxygenase-2 activation mediates the proangiogenic effect of nitric oxide in colorectal cancer. Clin. Cancer Res., 2004, 10(8), 2694-2704.
[http://dx.doi.org/10.1158/1078-0432.CCR-03-0192] [PMID: 15102673]
[31]
Hickok, J.R.; Thomas, D.D. Nitric oxide and cancer therapy: The emperor has NO clothes. Curr. Pharm. Des., 2010, 16(4), 381-391.
[http://dx.doi.org/10.2174/138161210790232149] [PMID: 20236067]
[32]
Martins, I.J. Single gene inactivation with implications to diabetes and multiple organ dysfunction syndrome. J. Cli. Epigenet., 2017, 3(24), 1-8.
[http://dx.doi.org/10.21767/2472-1158.100058]
[33]
Martins, I.J. Antimicrobial activity inactivation and toxic immune reactions induce Epilepsy in humans. J. Med. Discovery, 2017, 2(4), 1-7.
[34]
Xie, Y.; Zhang, J.; Ye, S.; He, M.; Ren, R.; Yuan, D.; Shao, C. SirT1 regulates radiosensitivity of hepatoma cells differently under normox-ic and hypoxic conditions. Cancer Sci., 2012, 103(7), 1238-1244.
[http://dx.doi.org/10.1111/j.1349-7006.2012.02285.x] [PMID: 22448750]
[35]
Lee, H-J.; Auh, Q-S.; Lee, Y-M.; Kang, S-K.; Chang, S-W.; Lee, D-S.; Kim, Y.C.; Kim, E.C. Growth inhibition and apoptosis-inducing effects of cudraflavone B in human oral cancer cells via MAPK, NF-κB, and SIRT1 signaling pathway. Planta Med., 2013, 79(14), 1298-1306.
[http://dx.doi.org/10.1055/s-0033-1350619] [PMID: 23881456]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy